Diabetic retinopathy(DR), the most common microvascular complication of diabetes, has become a leading cause of visual impairment and blindness across all age groups. The early diagnosis and severity assessment of DR rely on the precise evaluation of retinal microvascular alterations. The periarterial capillary-free zone(paCFZ), a physiological avascular region surrounding retinal arteries, has recently been recognized as an important biomarker reflecting the status of retinal microcirculation. Advances in optical coherence tomography angiography(OCTA)have enabled noninvasive, high-resolution quantification of the paCFZ, offering a novel approach for the early detection and stratification of DR. This review systematically summarizes the definition and developmental mechanism of the paCFZ, as well as its morphological characteristics across different stages of DR, with a particular focus on the advantages of OCTA in visualizing and quantifying the paCFZ. We further discuss the differential manifestations of the paCFZ in nonproliferative DR and proliferative DR, and its associations with retinal ischemia and oxygenation status. In addition, the potential clinical value of paCFZ in evaluating responses to anti-vascular endothelial growth factor(VEGF)therapy and predicting disease progression is summarized. Finally, the challenges in clinical translation and future research directions are addressed, aiming to provide theoretical support and new perspectives for early screening, risk stratification, and personalized management of DR.

ObjectiveTo investigate the effects of jatrorrhizine on endogenous metabolites and metabolic pathways in the mouse model of ulcerative colitis. MethodsThirty male C57BL/6J mice were randomly divided into the normal group， the model group， the low-dose and high-dose jatrorrhizine groups （0.04， 0.16 g·kg^-1）， and the mesalazine group （0.52 g·kg^-1）The mouse model of ulcerative colitis was established with 3% dextran sulfate sodium （DSS） and treated with different doses of jatrorrhizine by gavage. The changes in body weight， colon length， disease activity index （DAI）， and colonic histopathology were analyzed to evaluate the therapeutic effects of jatrorrhizine. UPLC-Q-TOF/MS was employed to determine the serum and fecal levels of metabolites in mice. Metabolomics methods were used to screen the differential metabolites， on the basis of which the potential therapeutic mechanism of jatrorrhizine on DSS-induced ulcerative colitis in mice was investigated. ResultsAfter intervention with jatrorrhizine， the model mice showed significantly decreased DAI（P<0.05，P<0.01）， recovered colon length，（P<0.05，P<0.01） and alleviated histopathology of the colon. The metabolomics study screened out 13 differential metabolites in the serum and 8 differential metabolites in the feces. The pathway enrichment analysis predicted three potential metabolic pathways： Biosynthesis of unsaturated fatty acids， phenylalanine， tyrosine and tryptophan biosynthesis， and phenylalanine metabolism. ConclusionJatrorrhizine may treat ulcerative colitis by regulating the biosynthesis and metabolism of amino acids and the synthesis of unsaturated fatty acids.

Objective: To investigate methods for constructing a high-quality instructional dataset for traditional Chinese medicine (TCM) mental disorders and to validate its efficacy. Methods: We proposed the Fine-Med-Mental-T&P methodology for constructing high-quality instruction datasets in TCM mental disorders. This approach integrates theoretical knowledge and practical case studies through a dual-track strategy. (i) Theoretical track: textbooks and guidelines on TCM mental disorders were manually segmented. Initial responses were generated using DeepSeek-V3, followed by refinement by the Qwen3-32B model to align the expression with human preferences. A screening algorithm was then applied to select 16 000 high-quality instruction pairs. (ii) Practical track: starting from over 600 real clinical case seeds, diagnostic and therapeutic instruction pairs were generated using DeepSeek-V3 and subsequently screened through manual evaluation, resulting in 4 000 high-quality practice-oriented instruction pairs. The integration of both tracks yielded the Med-Mental-Instruct-T&P dataset, comprising a total of 20 000 instruction pairs. To validate the dataset’s effectiveness, three experimental evaluations (both manual and automated) were conducted: (i) comparative studies to compare the performance of models fine-tuned on different datasets; (ii) benchmarking to compare against mainstream TCM-specific large language models (LLMs); (iii) data ablation study to investigate the relationship between data volume and model performance. Results: Experimental results demonstrate the superior performance of T&P-model fine-tuned on the Med-Mental-Instruct-T&P dataset. In the comparative study, the T&P-model significantly outperformed the baseline models trained solely on self-generated or purely human-curated baseline data. This superiority was evident in both automated metrics (ROUGE-L > 0.55) and expert manual evaluations (scoring above 7/10 across accuracy). In benchmark comparisons, the T&P-model also excelled against existing mainstream TCM LLMs (e.g., HuatuoGPT and ZuoyiGPT). It showed particularly strong capabilities in handling diverse clinical presentations, including challenging disorders such as insomnia and coma, showcasing its robustness and versatility. Data ablation studies showed that T&P-model performance had an overall upward trend with minor fluctuations when training data increased from 10% to 50%; beyond 50%, performance improvement slowed significantly, with metrics plateauing and approaching a saturation point. Conclusion This study has successfully constructed the specialized Med-Mental-Instruct-T&P instruction dataset for TCM mental disorders proposed the systematic Fine-Med-Mental-T&P methodology for its development, effectively addressing the critical challenge of high-quality, domain-specific data scarcity in TCM, and providing essential data support for developing intelligent TCM diagnostic and therapeutic systems.

Immune checkpoint inhibitors (ICIs) are widely used in the treatment of malignant tumors, and their related immune-related adverse events (irAEs) have attracted increasing attention. This study reports the diagnosis and treatment process of a case of immune cystitis in a patient with hepatobiliary tract malignant tumor after treatment with pembrolizumab. The patient was admitted to the hospital due to frequent urination, urgency of urination and dysuria for 1 month. Previous repeated anti-infection treatments were ineffective. Combined with medical history, laboratory tests, imaging findings, cystoscopy and pathological results, the patient was clinically diagnosed with ICIs-associated immune cystitis (Pembrolizumab) ultimately. The patient's symptoms significantly improved after treatment with glucocorticoids. This case reindicates that clinicians need to improve awareness of ICI-related urinary system irAEs. Early identification and timely intervention can significantly improve patient prognosis.

ObjectiveThis paper aims to investigate the material basis of the anti-inflammatory efficacy and mechanism of action of Bushen Tongdu prescription （BSTDP）. MethodsThe chemical components of BSTDP and its blood-absorbed components in vivo were systematically identified by using ultra-performance liquid chromatography-linear ion trap-electrostatic field orbitrap high-resolution mass spectrometry （UPLC-LIT-Orbitrap-MS）. Network pharmacology was employed to screen blood-absorbed bioactive components and potential targets of this formula. A protein-protein interaction （PPI） network of core targets was constructed to conduct enrichment analysis. Molecular docking was further utilized to verify the binding affinity between key components and targets. The inflammatory model was established and verified in vivo by using a transgenic zebrafish Tg （mpx： GFP）. At three days post-fertilization （3 dpf）， larvae of zebrafish were randomly assigned to blank group， model group， positive drug dexamethasone acetate group （75 μmol·L^-1）， and BSTDP groups with low， medium， and high doses （500， 1 000， and 2 000 mg·L^-1）. The distribution and quantity of neutrophils in the yolk sac region were observed under a fluorescence microscope. The mRNA expression levels of key genes in the toll-like receptor 4 （TLR4）/myeloid differentiation factor 88 （MyD88）/nuclear factor kappa-B （NF-κB） signaling pathway and inflammatory factors including interleukin （IL）-1β， IL-6， and tumor necrosis factor-α （TNF-α） were detected by Real-time quantitative polymerase chain reaction （Real-time PCR）. ResultsA total of 120 chemical components were identified in BSTDP， among which 26 original components were confirmed by using serum pharmacochemical methods. A total of 227 common targets linking rheumatoid arthritis （RA） and the blood-absorbed components were screened by network pharmacology. It is suggested that pseudobrucine， vomicine， sinapine， rehmannioside， cinnamyl alcohol glycoside， and methylephedrine exert anti-inflammatory effects by acting on core targets including protein kinase B1 （Akt1）， signal transducer and activator of transcription 3 （STAT3）， tumor necrosis factor （TNF）， TLR4， mitogen-activated protein kinase 14 （MAPK14）， and phosphatidylinositol-4，5-bisphosphate 3-kinase catalytic subunit α （PIK3CA）， thereby modulating multiple signaling pathways such as TLR4 and NF-κB. In vivo verification in zebrafish demonstrates that the maximum tolerable concentration of Bushen Tongdu Formula is 2 000 mg·L^-1. Compared to those in the blank group， zebrafish in the model group showed a significantly higher number of neutrophils in the yolk sac region （P<0.01） and rising mRNA levels of TLR4， MyD88， NF-κB， TNF-α， IL-6， and IL-1β （P<0.01）. Compared to that in the model group， the number of neutrophils was significantly reduced in BSTDP groups with medium and high doses， as well as the dexamethasone acetate group （P<0.05， P<0.01）. There was no statistically significant difference in the low dose group. The mRNA expression levels of TLR4， MyD88， NF-κB， TNF-α， IL-6， and IL-1β were significantly down-regulated （P<0.05， P<0.01）. ConclusionThis paper identifies the material basis of the efficacy of BSTDP， demonstrating that the formula can exert an anti-inflammatory effect through the TLR4/MyD88/NF-κB signaling pathway. The results provide scientific experimental evidence for its further clinical application.

Puji Xiaoduyin， a specialized formula for the swollen-head epidemic， was recorded in the Catalogue of Ancient Classical Formula （the Second Batch）-Han Medicine， published in September 2023. It had been inherited and developed by medical experts of successive generations and passed down to this day. This paper sorted out the historical evolution of this formula using bibliometric methods. It also comprehensively analyzed key information on the formula name， historical origin， drug dosage， herb origin， processing methods， decocting methods， function， and clinical applications. Additionally， this paper analyzed the application of this formula in both modern and ancient times. Results showed that the formula was first recorded as "Puji Xiaodu Yinzi" in LI Dongyuan's Proven Formulas written by LI Gao from the Jin dynasty. The medicinal composition and dosage were： Scutellariae Radix and Coptidis Rhizoma （20.65 g each）， Ginseng Radix et Rhizoma 12.39 g， Scrophulariae Radix， Citri Reticulatae Pericarpium， and Glycyrrhizae Radix et Rhizoma （8.26 g each）， Forsythiae Fructus， Arctii Fructus， Isatidis Radix， and Lasiosphaera Calvatia （4.13 g each）， Bombyx Batryticatus and Cimicifugae Rhizoma （2.891 g each）， Bupleuri Radix and Platycodonis Radix （8.26 g each）. These medicines were grounded to fine powder. One dose， including 20.65 g of the powder， was mixed with 600 mL of water and decocted to 300 mL. After abandoning slag， the medicine should be taken warm frequently. In the formula， Bombyx Batryticatus is stir-fired. With the effect of dispersing wind and clearing heat， removing stagnation and dissipating mass， the formula is specialized in swollen-head epidemic， pestilence， red and swelling head， face， and neck， dry mouth and tongue， as well as other diseases resulting from toxic heat stagnated in the upper jiao. The formula is widely used in treating diseases involving the respiratory， dermal， ophthalmologic， otolaryngologic， and nervous systems. The formula is most frequently used for respiratory diseases， with a wide range of symptoms including parotitis/mumps （66 times）， followed by tonsillitis （28 times）. In conclusion， the broadly applied formula has accurate efficacy and great development value.

ObjectiveThis paper aims to investigate the material basis of the anti-inflammatory efficacy and mechanism of action of Bushen Tongdu prescription （BSTDP）. MethodsThe chemical components of BSTDP and its blood-absorbed components in vivo were systematically identified by using ultra-performance liquid chromatography-linear ion trap-electrostatic field orbitrap high-resolution mass spectrometry （UPLC-LIT-Orbitrap-MS）. Network pharmacology was employed to screen blood-absorbed bioactive components and potential targets of this formula. A protein-protein interaction （PPI） network of core targets was constructed to conduct enrichment analysis. Molecular docking was further utilized to verify the binding affinity between key components and targets. The inflammatory model was established and verified in vivo by using a transgenic zebrafish Tg （mpx： GFP）. At three days post-fertilization （3 dpf）， larvae of zebrafish were randomly assigned to blank group， model group， positive drug dexamethasone acetate group （75 μmol·L^-1）， and BSTDP groups with low， medium， and high doses （500， 1 000， and 2 000 mg·L^-1）. The distribution and quantity of neutrophils in the yolk sac region were observed under a fluorescence microscope. The mRNA expression levels of key genes in the toll-like receptor 4 （TLR4）/myeloid differentiation factor 88 （MyD88）/nuclear factor kappa-B （NF-κB） signaling pathway and inflammatory factors including interleukin （IL）-1β， IL-6， and tumor necrosis factor-α （TNF-α） were detected by Real-time quantitative polymerase chain reaction （Real-time PCR）. ResultsA total of 120 chemical components were identified in BSTDP， among which 26 original components were confirmed by using serum pharmacochemical methods. A total of 227 common targets linking rheumatoid arthritis （RA） and the blood-absorbed components were screened by network pharmacology. It is suggested that pseudobrucine， vomicine， sinapine， rehmannioside， cinnamyl alcohol glycoside， and methylephedrine exert anti-inflammatory effects by acting on core targets including protein kinase B1 （Akt1）， signal transducer and activator of transcription 3 （STAT3）， tumor necrosis factor （TNF）， TLR4， mitogen-activated protein kinase 14 （MAPK14）， and phosphatidylinositol-4，5-bisphosphate 3-kinase catalytic subunit α （PIK3CA）， thereby modulating multiple signaling pathways such as TLR4 and NF-κB. In vivo verification in zebrafish demonstrates that the maximum tolerable concentration of Bushen Tongdu Formula is 2 000 mg·L^-1. Compared to those in the blank group， zebrafish in the model group showed a significantly higher number of neutrophils in the yolk sac region （P<0.01） and rising mRNA levels of TLR4， MyD88， NF-κB， TNF-α， IL-6， and IL-1β （P<0.01）. Compared to that in the model group， the number of neutrophils was significantly reduced in BSTDP groups with medium and high doses， as well as the dexamethasone acetate group （P<0.05， P<0.01）. There was no statistically significant difference in the low dose group. The mRNA expression levels of TLR4， MyD88， NF-κB， TNF-α， IL-6， and IL-1β were significantly down-regulated （P<0.05， P<0.01）. ConclusionThis paper identifies the material basis of the efficacy of BSTDP， demonstrating that the formula can exert an anti-inflammatory effect through the TLR4/MyD88/NF-κB signaling pathway. The results provide scientific experimental evidence for its further clinical application.

Puji Xiaoduyin， a specialized formula for the swollen-head epidemic， was recorded in the Catalogue of Ancient Classical Formula （the Second Batch）-Han Medicine， published in September 2023. It had been inherited and developed by medical experts of successive generations and passed down to this day. This paper sorted out the historical evolution of this formula using bibliometric methods. It also comprehensively analyzed key information on the formula name， historical origin， drug dosage， herb origin， processing methods， decocting methods， function， and clinical applications. Additionally， this paper analyzed the application of this formula in both modern and ancient times. Results showed that the formula was first recorded as "Puji Xiaodu Yinzi" in LI Dongyuan's Proven Formulas written by LI Gao from the Jin dynasty. The medicinal composition and dosage were： Scutellariae Radix and Coptidis Rhizoma （20.65 g each）， Ginseng Radix et Rhizoma 12.39 g， Scrophulariae Radix， Citri Reticulatae Pericarpium， and Glycyrrhizae Radix et Rhizoma （8.26 g each）， Forsythiae Fructus， Arctii Fructus， Isatidis Radix， and Lasiosphaera Calvatia （4.13 g each）， Bombyx Batryticatus and Cimicifugae Rhizoma （2.891 g each）， Bupleuri Radix and Platycodonis Radix （8.26 g each）. These medicines were grounded to fine powder. One dose， including 20.65 g of the powder， was mixed with 600 mL of water and decocted to 300 mL. After abandoning slag， the medicine should be taken warm frequently. In the formula， Bombyx Batryticatus is stir-fired. With the effect of dispersing wind and clearing heat， removing stagnation and dissipating mass， the formula is specialized in swollen-head epidemic， pestilence， red and swelling head， face， and neck， dry mouth and tongue， as well as other diseases resulting from toxic heat stagnated in the upper jiao. The formula is widely used in treating diseases involving the respiratory， dermal， ophthalmologic， otolaryngologic， and nervous systems. The formula is most frequently used for respiratory diseases， with a wide range of symptoms including parotitis/mumps （66 times）， followed by tonsillitis （28 times）. In conclusion， the broadly applied formula has accurate efficacy and great development value.

The Golgi body, a core organelle in eukaryotic cells, plays a critical role in protein modification, sorting, vesicular transport, and serves as a key site for lipid synthesis and glycosylation. Glucose and lipid metabolism are central processes for cellular energy maintenance and biosynthesis, and are closely linked to Golgi function. Recent studies have revealed the extensive involvement of the Golgi body in regulating glucose and lipid metabolism, where maintaining its structural and functional homeostasis is crucial for normal physiological activity. Under various stress conditions such as acidosis, hypoxia, and nutrient deficiency, the Golgi body undergoes structural and functional disruption, leading to Golgi stress. This in turn activates specific signaling pathways, such as those mediated by the cAMP-responsive element binding protein 3 (CREB3) and proteoglycans, to alleviate Golgi stress and enhance Golgi function. Golgi stress contributes to glucose and lipid metabolic disorders by affecting the activity of insulin receptors, glucose transporters, and lipid metabolism-related enzymes. For example, Golgi stress triggers the cleavage and release of the active fragment of CREB3, which enters the nucleus and upregulates the transcription of ADP-ribosylation factor 4 (ARF4) and key gluconeogenic enzymes, including phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase). ARF4 promotes vesicle retrograde transport between the Golgi and endoplasmic reticulum, maintains secretory capacity, and enhances hepatic glucose output. This pathway is particularly active under high-fat or lipotoxic stress, leading to fasting hyperglycemia. When damaged Golgi components accumulate beyond a tolerable threshold, the cell initiates an autophagic response, selectively encapsulating the damaged Golgi into autophagosomes, which then fuse with lysosomes to form autolysosomes, leading to Golgiphagy. This process results in the degradation and clearance of damaged Golgi, thereby regulating Golgi quantity, quality, and function. Golgiphagy also plays a significant role in regulating glucose and lipid metabolism. For instance, under high-glucose conditions, autophagic flux may be suppressed, impairing the timely clearance and renewal of damaged Golgi, compromising its normal function, and further exacerbating glucose metabolism disorders. Additionally, Golgiphagy may participate in lipid degradation and influence lipid synthesis and transport. Research indicates that Golgi stress and Golgiphagy play important roles in glucose and lipid metabolism-related diseases. For example, the leucine zipper protein (LZIP) under Golgi stress conditions can promote hepatic steatosis. In mouse primary cells and human tissues, LZIP induces the expression of apolipoprotein A-IV (APOA4), which increases peripheral free fatty acid uptake, resulting in lipid accumulation in the liver and contributing to the development of fatty liver disease. This review systematically outlines the structure and function of the Golgi apparatus, the molecular regulatory mechanisms of Golgi stress and Golgiphagy, and their synergistic roles. It further elaborates on how Golgi stress and Golgiphagy participate in the regulation of glucose and lipid metabolism, discusses their clinical significance in related diseases such as diabetes, fatty liver disease, and obesity, and highlights potential novel therapeutic strategies from the perspective of Golgi-targeted medicine. Finally, this article addresses the challenges and future directions in Golgi-targeted interventions, aiming to advance the clinical translation of such strategies and foster breakthroughs in the treatment of glucose and lipid metabolism-related disorders.

Organoid-on-a-chip technology represents a promising interdisciplinary advancement that merges two cutting-edge biomedical platforms: stem cell-derived organoids and microfluidics-based organ-on-a-chip systems. Organoids are self-organizing three-dimensional (3D) cell cultures that mimic the key structural and functional features of in vivo organs. However, traditional organoid culture systems are often static, lacking dynamic environmental cues and suffering from limitations such as batch-to-batch variability, low stability, and low throughput. Organ-on-a-chip platforms, by contrast, utilize microfluidic technologies to simulate the dynamic physiological microenvironment of human tissues and organs, enabling more controlled cell growth and differentiation. By integrating the advantages of organoids and organ-on-a-chip technologies, organoid-on-a-chip systems transcend the limitations of conventional 3D culture models, offering a more physiologically relevant and controllable in vitro platform. In organoid-on-a-chip systems, stem cells or pre-formed organoids are cultured in micro-engineered environments that mimic in vivo conditions, enabling precise control over fluid flow, mechanical forces, and biochemical cues. Specifically, these platforms employ advanced strategies including bio-inspired 3D scaffolds for structural support, precise spatial cell patterning via 3D bioprinting, and integrated biosensors for real-time monitoring of metabolic activities. These synergistic elements recreate complex extracellular matrix signals and ensure high structural fidelity. Based on structural complexity, organoid-on-a-chip systems are classified into single-organoid and multi-organoid types, forming a trajectory from unit biomimicry to systemic simulation. Single-organoid chips focus on highly biomimetic units by integrating vascular, immune, or neural functions. Multi-organoid chips simulate inter-organ crosstalk and systemic homeostasis, advancing complex disease modeling and PK/PD evaluation. This emerging technology has demonstrated broad application potential in multiple fields of biomedicine. Organoid-on-a-chip systems can recapitulate organ developmentin vitro, facilitating research in developmental biology. They mimic organ-specific physiological activities and mechanisms, showing promising applications in regenerative medicine for tissue repair or replacement. In disease modeling, they support the reconstruction of models for neurodegenerative, inflammatory, infectious, metabolic diseases, and cancers. These platforms also enable in vitro drug testing and pharmacokinetic studies (ADME). Patient-derived chips preserve genetic and pathological features, offering potential for precision medicine. Additionally, they reduce species differences in toxicology, providing human-relevant data for environmental, food, cosmetic, and drug safety assessments. Despite progress, organoid-on-a-chip systems face challenges in dynamic simulation, extracellular matrix (ECM) variability, and limited real-time 3D imaging, requiring improved materials and the integration of developmental signals. Current bottlenecks also include the high technical threshold for automation and the lack of standardized validation frameworks for regulatory adoption. Meanwhile, the concept of a “human-on-a-chip” has been proposed to mimic whole-body physiology by integrating multiple organoid modules. This approach enables systemic modeling of drug responses and toxicity, with the potential to reduce animal testing and revolutionize drug development. Future advancements in bio-responsive hydrogels and flexible biosensors will further empower these platforms to bridge the gap between bench-side research and personalized clinical interventions. In conclusion, organoid-on-a-chip technology offers a transformative in vitro model that closely recapitulates the complexity of human tissues and organ systems. It provides an unprecedented platform for advancing biomedical research, clinical translation, and pharmaceutical innovation. Continued development in biomaterials, microengineering, and analytical technologies will be essential to unlocking the full potential of this powerful tool.